Alkynes Lithium

With higher homologs e.g., propynyl, butynyl), 3j5-hydroxyandrost-5-en-17-one does not react well with the alkyne and potassium r-butoxide, or with the lithium alkyne in tetrahydrofuran. However, satisfactory results are obtained by use of the alkynylmagnesium bromide in tetrahydrofuran, ... 

Alkynylzinc chlorides are useful imermedtates in Pd°-catalysed couplings with vinyl, heteroaryl [56) and acyl halides [89] tsee Chaps. V and X). The conversion of lithium alkyn-vlides into alkynylzinc halides with anhydrous zinc chloride in THF proceeds smoothly and quantitatively under mild conditions. 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

It is possible to prepare unsymmetrical conjugated diynes by modifying this procedure . Treatment of 1-alkynyldisiamylborane (36) with lithium alkyne gives the corresponding borate complex 37, and when this reacts with iodine at — 78 °C, the diyne 38 is obtained in good yield. For example, 3,5-dodecadiyne (38 R = Et,... 

Lithium alkynes [1, 96, before references]. Pattison and Dear9 found the reagent... 

Liebermann-Burchardt reaction, 137, 138 ( )-Lindestrene, 141 N-Lithioethylenediamine, 239 3-Lithio-l-trimethylsilylpropyne, 239-241 Lithium, 208, 255 Lithium acetylide, 241, 288 Lithium acetylide -ethylenediamine, 208 Lithium-Alkylamine reduction, 241-242 Lithium alkynes, 52... 

As with cyanide, Sn2 reactions of alkyne anions can be done with substrates other than halides or sulfonate esters. Epoxides are opened by acetylides at the less sterically hindered carbon to give an alkynyl alcohol. A synthetic example is the reaction of epoxide 38 with the indicated lithium alkyne anion gave an 85% yield of 39, an intermediate in the Sinha et al. synthesis of squamotacin.49... 

Tin alkynes rearrange to yield allene products in much the same way as do lithium alkynes, except that the reaction involves a radical mechanism. It is very similar to the reaction of allyl stannanes with alkyl halides, which substitutes the allyl group. Similar reactions are reported for allyl derivatives of cobalt, rhodium and iridium, but this work has not been extended to alkyne derivatives. 

Conjugated diynes (cf. 5, 346). A convenient route to these substances, both symmetrical and unsymmetrical, has been developed by Sinclair and Brown. Treatment of 1-alkynyldisiamylboranes with lithium alkynes forms an ate complex (I), which on reaction with iodine at - 78" in THF gives a diync (2). It is also possible to carry out this synthesis without isolation of the l-alkynyl-... 

Another method of preparing aminoalkynylpyridines involves the reaction of lithium alkynes with pyridyl ketones. Thus, 4-diethylamino-1-phenyl-1-(2-pyridyl)-2-butyn-l-ol (IX-2S4) is obtained by the reaction of lithium amide with diethylamino-2-propyne followed by 2-benzoylpyridine. Similarly, the use of 3-... 

Substituted allenes are obtained from the reaction of propargyl silanes (prepared from lithium alkynes and trimethylsilylmethyl chloride ) and electrophiles. An exocyclic allene is produced when this reaction involves ring closure, a method which has been applied in a biomimetic steroid synthesis (Scheme 16). ° If the corresponding trimethylsilylalkyne is used a D-homosteroid system is obtained. ... 

Seleno-i3-lactams 39 are obtained from lithium alkyne selenoates 38 and azomethines. The reaction most likely proceeds via a [2+2] cycloaddition because 38 is in equilibrium with PhHC=C=Se ... 

The sex pheromone of Trogoderma inclusum is a mixture of the branched unsaturated ester (139) and its corresponding alcohol (138) and aldehyde (Scheme 26). Two syntheses giving raC mlC Material (113, 114) used the Wittig reaction to form the Z double bond. Optically active products were obtained by Mori (775) via the alkyl bromide-lithium alkyne coupling reaction followed by catalytic reduction. In a similar manner, Rossi and Carpita (776) prepared optically active S (138), its JS -isomer and the corresponding Z- and -aldehydes. 

The regioselectivity of the addition of terminal alkynes to epoxides is improved, when the reagents prepared from the lithiated alkynes and either trifluoroborane or chlorodiethyl-aluminum arc employed (M. Yamaguchi, 1983 S. Danishefsky, 1976). (Ethoxyethynyl)lithium-trifluoroborane (1 1) is a convenient reagent for converting epoxides to y-lactones (M. Naka-tsuka, 1990 see p. 327f. cf. S. Danishefsky, 1976). 

Propargylic alcohol, after lithiation, reacts with CO2 to generate the lithium carbonate 243, which undergoes oxypalladation. The reaction of allyl chloride yields the cyclic carbonate 244 and PdC. By this reaction hydroxy and allyl groups are introduced into the triple bond to give the o-allyl ketone 245[129]. Also the formation of 248 from the keto alkyne 246 with CO2 via in situ formation of the carbonate 247 is catalyzed by Pd(0)[130]. 

A useful alternative to catalytic partial hydrogenation for converting alkynes to alkenes IS reduction by a Group I metal (lithium sodium or potassium) m liquid ammonia The unique feature of metal-ammonia reduction is that it converts alkynes to trans alkenes whereas catalytic hydrogenation yields cis alkenes Thus from the same alkyne one can prepare either a cis or a trans alkene by choosing the appropriate reaction conditions... 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

One way to generate carbanions is to combine an acidic molecule with one equivalent of a very strong base, such as n-butyl lithium (n-BuLi). For example, reaction of the alkyne shown below with n-BuLi leads to a carbanion of formula CsH, 02 , which then undergoes an Sn2 reaction with n-propyl bromide (n-PrBr),... 

An alternative method for the conversion of an alkyne to an alkene uses sodium or lithium metal as the reducing agent in liquid ammonia as solvent. This method is complementary to the Lindlar reduction because it produces... 

Mechanism of the lithium/ ammonia reduction of an alkyne to produce a trans alkene. 

O Lithium metal donates an electron to the alkyne to give an anion radical. .. ... 

The product i n this case is a cis-disubstituted alkene, so the fi rst question is, " What is an immediate precursor of a cis-disubstituted alkene " We know that an alkene can be prepared from an alkyne by reduction and that the right choice of experimental conditions will allow us to prepare either a trans-disubstituted alkene (using lithium in liquid ammonia) ora cis-disubstituted alkene (using catalytic hydrogenation over the Lindlar catalyst). Thus, reduction of 2-hexyne by catalytic hydrogenation using the Lindlar catalyst should yield cis-2-hexene. 

Alkynes can be reduced to yield alkenes and alkanes. Complete reduction of the triple bond over a palladium hydrogenation catalyst yields an alkane partial reduction by catalytic hydrogenation over a Lindlar catalyst yields a cis alkene. Reduction of (he alkyne with lithium in ammonia yields a trans alkene. 

Liquid chromatography. 432 Lithium, reaction with alkynes, 269-270... 

Among the tasks remaining is the replacement of the C-16 hydroxyl group in 16 with a saturated butyl side chain. A partial hydrogenation of the alkyne in 16 with 5% Pd-BaS04 in the presence of quinoline, in methanol, followed sequentially by selective tosylation of the primary hydroxyl group and protection of the secondary hydroxyl group as an ethoxyethyl ether, affords intermediate 17 in 79% overall yield from 16. Key intermediate 6 is formed in 67 % yield upon treatment of 17 with lithium di-n-butylcuprate. 

Fleming has shown (2) that the cuprate reagent (Chapter 8) derived from dimethylphenylsilyl lithium and copper(t) cyanide (molar ratio 2 1) adds regioselectively in an overall syn manner to terminal alkynes, the silyl moiety becoming attached to the terminal carbon atom (variation in reagent... 

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